Significance HIV transmission to infants by breast feeding after maternally acquired anti-HIVantibodies decline is well documented. Neonatal vaccination may reduce HIV transmission to children in developing nations where safe alternatives to breast feeding are not available. However, a safe and economical anti-HIV vaccine for neonates must also elicit immunity in the presence of maternal anti-HIV antibodies. Objectives Infection of newborn rhesus macaques with simian immunodeficiency virus is a well-established model for pediatric HIV infection and AIDS. This pilot study evaluated whether proviral DNA from the virulence-attenuated SHIV-33 (virus derived from a molecular clone that consists the HIV-1 SF-33 envelope gene in an otherwise SIV genome) could establish infection in neonates with transplacentally acquired anti-SIV antibodies. Results Three pregnant rhesus macaques were immunized twice intramuscularly during pregnancy with whole-inactivated SIV in adjuvant. After boosting, the dams produced high titer SIV-specific serum antibodies which were transferred to their infants. Four neonates with no anti-SIV antibodies served as controls. All seven infants were inoculated intramuscularly with 100 ug of SHIV-33 proviral DNA within 3 days of birth. Five of the seven infants became infected with SHIV-33 two infants with anti-SIV antibodies and three infants with no SIV antibodies. Virus levels remained low in all but one SHIV-infected animal and none developed any clinical signs of disease by 24 weeks of age. Thus, transplacentally acquired anti-SIV antibodies did not interfere with infection induced by inoculation of neonates with SHIV-33 proviral DNA. These results suggest that a live-attenuated HIV DNA might be developed as a vaccine that could establish infection even in infants with maternally-derived anti-HIV antibodies. Future Directions At 1 year of age each of the five animals infected with live-attenuated SHIV-33 will be inoculated orally with SIVmac239 to determine whether neonatal vaccination can provide long-term protection against virulent SIV. KEYWORDS Pediatric simian AIDS, oral SIV transmission, perinatal HIV transmission, neonatal immunization, live-attenuated vaccine